In an essay on this site, I wrote the following:
QUOTE: Mutat Res. 2002 Sep 30;506-507:9-20. "Comments on the history and importance of aromatic and heterocyclic amines in public health." Weisburger JH.
"The carcinogenic risk of aromatic amines in humans was first discovered when a physician related the occurrence of urinary bladder cancer to the occupation of his patients. They were employed in the dyestuff industry, chronically exposed to large amounts of intermediate arylamines�?Epidemiological data suggest that meat eaters may have a higher risk of breast and colon cancer. HCAs induced cancer in rats in these organs and also in the prostate and the pancreas. In addition, there is some evidence that they affect the vascular system. The formation of HCAs during cooking can be decreased by natural and synthetic antioxidants, by tryptophan or proline, or by removing the essential creatine through brief microwave cooking prior to frying or broiling. The amounts of HCAs in cooked foods are small, but other components in diet such as omega-6-polyunsaturated oils have powerful promoting effects in target organs of HCAs. On the other hand, the action of HCAs may be decreased by foods containing antioxidants, such as vegetables, soy, and tea�?Possibly, the carcinogenic effect of HCAs is accompanied by the presence of reactive oxygen species (ROS), which are also inhibited by antioxidants..."
Finally, from a recent report: "...The researchers couldn't explain why eating more animal fat was associated with breast cancer risk. It may be that factors other than fat are involved. For instance, grilling red meat can create cancer-causing chemicals�?Earlier studies had suggested one reason for the increased cancer risk, relating this to the heterocyclic amines (HCAs) that form when red meat is cooked at high temperatures (like frying and grilling), especially well-done. In laboratory studies, HCAs bond to estrogen receptors and create estrogen-like effects. In earlier research with
women past menopause, those who consistently ate hamburger, beef steak and bacon very well done thus getting high levels of HCAs -had more
than four times the breast cancer risk in comparism with women who consumed these meats raw or medium done�?Like many carcinogens, HCAs have to be activated to be able to damage our DNA and pose cancer risk..."
Source: http://www.tribune.com.ng/22032007/hlt2.html UNQUOTE.
I just came across this new evidence, which supports the findings above:
Cancer Res. 2007 Dec 1;67(23):11455-62.
Abstract: During the cooking of meat, mutagenic and carcinogenic heterocyclic amines are formed, the most abundant of which, 2-amino-1-methyl-6-phenylimidazo[4-5-b]pyridine (PhIP), induces tumors of the prostate, colon, and mammary gland in rats. Humans consuming cooked meat are exposed to PhIP on a daily basis, yet few studies have assessed the effects of PhIP at dietary relevant concentrations. In addition to its genotoxic properties, recent studies have shown that PhIP can activate estrogen receptor-mediated signaling pathways at doses that are similar to those that may be present in the body following consumption of a cooked meat meal. In the present study, we examined whether such doses of PhIP can affect estrogen receptor-independent signal transduction via the mitogen-activated protein kinase (MAPK) extracellular signal-related kinase (ERK) pathway to influence proliferation and migration in the human mammary epithelial cell line MCF10A and the prostate cancer cell line PC-3. At doses shown to have a proliferative effect on MCF10A cells (10(-11)-10(-7) mol/L), PhIP induced a rapid, transient increase in phosphorylation of both MAPK/ERK kinase 1/2 and ERKs. Inhibition of this pathway significantly reduced the PhIP-induced proliferation of MCF10A cells and the migration of PC-3 cells. The data presented here show that levels of PhIP that approximate to human dietary exposure stimulate cellular signaling pathways and result in increased growth and migration, processes linked to the promotion and progression of neoplastic disease. These findings provide strong evidence that PhIP acts as a tumor initiator and promoter and that dietary exposure to this compound could contribute to carcinogenesis in humans.
And:
Cancer Res. 2007 Oct 1;67(19):9597-602.
TITLE: "The cooked meat derived genotoxic carcinogen 2-amino-3-methylimidazo[4,5-b]pyridine has potent hormone-like activity: mechanistic support for a role in breast cancer."
And:
Toxicol Lett. 2007 Feb 5;168(3):269-77. Epub 2006 Nov 16.
Abstract: Formed during the cooking of meat, the heterocyclic amine 2-amino-1-methyl-6-phenylimidazo[4-5-b]pyridine (PhIP) is mutagenic and carcinogenic. Although the metabolism and mutational effects of PhIP are well defined, the early cellular and genomic events by which it can induce neoplastic transformation are not yet fully characterised. These early cellular responses to genotoxic doses of PhIP were examined in a human mammary epithelial cell, MCF10A. Using Western blotting, PhIP was shown to induce expression of the DNA damage response proteins p53 and p21(WAF1/CIP1), and to inhibit cell growth while activating G1 cell cycle checkpoint, a consequence of PhIP-induced DNA damage. Using low doses of PhIP (previously shown to activate oestrogenic signalling), PhIP increased proliferation in the oestrogen receptor (ER)-negative MCF10A cell line and to activate the mitogen-activated protein kinase (MAPK) pathway. Inhibition of this pathway significantly reduced the PhIP-induced cell growth of MCF10A cells. The work presented here suggests that, further to its genotoxic properties, at levels close to human exposure PhIP stimulates cellular signalling pathways that are linked to the promotion and progression of neoplastic disease. It is possible that a combination of these DNA damaging and growth promoting properties provide a mechanism for the tumourigenicity of PhIP, and may be key determinants for the tissue specificity of PhIP-induced carcinogenesis.
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